2-241188700-G-T

Variant names:

• chr2-241188700-G-T
• ENST00000274979.12:c.89G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000274979.12(ANO7):​c.89G>T​(p.Arg30Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,306 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R30Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ANO7 ENST00000274979.12 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.23

Genes affected

ANO7 (HGNC:31677): (anoctamin 7) This prostate-specific gene encodes a cytoplasmic protein, as well as a polytopic membrane protein which may serve as a target in prostate cancer diagnosis and immunotherapy. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04332441).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANO7	NM_001370694.2	c.-74G>T		5_prime_UTR_variant	Exon 1 of 25	ENST00000674324.2	NP_001357623.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANO7	ENST00000274979.12	c.89G>T	p.Arg30Leu	missense_variant	Exon 1 of 25	1		ENSP00000274979.8
ANO7	ENST00000674324	c.-74G>T		5_prime_UTR_variant	Exon 1 of 25		NM_001370694.2	ENSP00000501393.1
ANO7	ENST00000402530	c.-74G>T		5_prime_UTR_variant	Exon 1 of 4	1		ENSP00000383985.4
ANO7	ENST00000402430	c.-74G>T		5_prime_UTR_variant	Exon 1 of 22	5		ENSP00000385418.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461306 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726998

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	2.3
DANN	Benign	0.81
DEOGEN2	Benign	0.041	.;T;.
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.47	T;T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.043	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;N;N
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-2.6	D;N;N
REVEL	Benign	0.091
Sift	Uncertain	0.026	D;D;D
Sift4G	Benign	0.20	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.090
MutPred		0.41		Gain of helix (P = 0.0082);Gain of helix (P = 0.0082);Gain of helix (P = 0.0082);
MVP		0.16
MPC		0.14
ClinPred		0.054	T
GERP RS		-4.4
Varity_R		0.048
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-242128115;